Despite technological advances and improved care delivery, antibiotic resistance and healthcare associated infections continue to plague our health system. The applicant, Dr. Aaron Milstone, is a Pediatric Infectious Diseases Physician and Epidemiologist who had focused his career on the prevention of antibiotic resistance and healthcare-associated infections. This K24 application builds on his career goals of translating laboratory and epidemiologic observations into patient- and population-level interventions and will prepare him and his trainees to identify, develop, and test new strategies to prevent infections and antibiotic resistance. The specific research aims are to: 1) identify risk factors for and develop a predictive model of carbapenem- resistant organism colonization and transmission in hospitalized patients, 2) identify bacterial communities, bacterial genes, and patient clinical characteristics associated with resistance to S. aureus nasal colonization in hospitalized neonates at risk for S. aureus acquisition from parents with known S. aureus colonization, and 3) determine whether bacterial culture stewardship reduces antibiotic use and resistance. The proposed projects will build on existing funded projects and collaborations in microbiome, genomics, and implementation science, expand the Dr. Milstone's knowledge in these areas, and make him a more effective PI and patient oriented research mentor.